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Hepatocarcinogenesis in the Context of Strain Differences in Energy Metabolism Between Inbred Strains of Mice (C57BL/6J and C3H/He)

  • Monika Chabicovsky
  • Katrin Staniek
  • Walter Rossmanith
  • Wilfried Bursch
  • Hans Nohl
  • Rolf Schulte-Hermann
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 500)

Abstract

Liver neoplasia in mice is one of the most frequent tumor target tissue endpoints observed in 2-year carcinogenicity studies of the US National Toxicology Program (NTP). B6C3F1 mice are the hybrids of male C3H/He, which are highly sensitive (hepatomas in 7291% at 14 months), and C57B1/6J females, which exhibit a low susceptibility to spontaneous and chemically induced hepatocarcinogenesis (Heston, 1963; Drinkwater and Bennett, 1991; Dragani et al. 1995; Wastl et al. 1998). Thus, the validity of mouse liver tumor endpoint in assessing the potential hazards of chemical exposure to humans is a controversial issue, since tumor susceptibility varies even within inbred strains of mice. Therefore our studies aimed to elucidate strain specifities that may modulate tumor development to improve the assessment for the relevance of mouse liver tumor induction in toxicological testing of chemicals.

Keywords

Strain Difference Mitochondrial Uncouple UCP2 Expression National Toxicology Program B6C3F1 Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Berry, M. J., Grieco, D., Taylor, B. A., Maia, A. L., Kieffer, J. D., Beamer, W., Glover, E., Poland, A., and Larsen, P. R., 1993, Physiological and genetic analyses of inbred mouse strains with a type I iodothyronine 5’ deiodinase deficiency J Clin. Inve st. 92:1517–1528.PubMedCrossRefGoogle Scholar
  2. Brand, M. D., Hafner, R P., and Brown, G. C., 1988, Control of respiration in non-phosphorylating mitochondria is shared between the proton leak and the respiratory chain, Biochem. J. 255:535–539.PubMedGoogle Scholar
  3. Chance, B., Sies, H., and Boveris, A., 1979, Hydroperoxide metabolism in mammalian organs, Physiol. Rev. 59:527–605.Google Scholar
  4. Chavin, K. D., Yang, S., Lin, H. Z., Chatham, J., Chacko, V. P., Hoek, J. B., Walajtys Rode, E., Rashid, A., Chen, C. H., Huang, C. C., Wu, T. C., Lane, M. D., and Diehl, A. M., 1999, Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion, J Biol. Chem. 274:5692–5700.PubMedCrossRefGoogle Scholar
  5. Curcio, C., Lopes, A. M., Ribeiro, M. O., Francoso, O. A., Jr., Carvalho, S. D., Lima, F. B., Bicudo, J. E., and Bianco, A. C., 1999, Development of compensatory thermogenesis in response to overfeeding in hypothyroid rats, Endocrinology 140:3438–3443.PubMedCrossRefGoogle Scholar
  6. Dombrowski, F., Klotz, L., Hacker, H. J., Li, Y., Klingmuller, D., Brix, K., Herzog, V., and Bannasch, P., 2000, Hyperproliferative hepatocellular alterations after intraportal transplantation of thyroid follicles, Am J. Pathol. 156:99–113.PubMedCrossRefGoogle Scholar
  7. Dragani, T. A., Manenti, G., Gariboldi, M., De Gregorio, L., and Pierotti, M. A., 1995, Genetics of liver tumor susceptibility in mice, Toxicol. Lett. 83:613–619.CrossRefGoogle Scholar
  8. Drinkwater, N. R, and Bennett, L. M., 1991, Genetic control of carcinogenesis in experimental animals, Prog. Exp. Tumor. Res. 33:1–20.PubMedGoogle Scholar
  9. Fleury, C., Neverova, M., Collins, S., Raimbault, S., Champigny, O., Levi Meyrueis, C., Bouillaud, F., Seldin, M. F., Survit, R. S., Ricquier, D., and Warden, C. H., 1997, Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia, Nat. Genet. 15:269–272.Google Scholar
  10. Harper, M. E., and Brand, M. D., 1993, The quantitative contributions of mitochondrial proton leak and ATP turnover reactions to the changed respiration rates of hepatocytes from rats of different thyroid status, J. Biol. Chem. 268:14850–14860.PubMedGoogle Scholar
  11. Heston, W. E., 1963, Genetics of neoplasia, in: Methodology in mammalian genetics (W. J. Burdette, ed.), Holden-Day, San Francisco, pp. 247–268.Google Scholar
  12. Horst, C., Rokos, R, and Seitz, H. J., 1989, Rapid stimulation of hepatic oxygen consumption by 3,5-diiodo-L-thyronine, Biochem. J. 261:945–950.PubMedGoogle Scholar
  13. Leffert, R L., and Alexander, N. M., 1976, Thyroid hormone metabolism during liver regeneration in rats, Endocrinology 98:1241–1247.PubMedCrossRefGoogle Scholar
  14. Lemaire, M., Baeyens, W., de Saint Georges, L., and Baugnet Mahieu, L., 1981, Thyroid influence on the growth of hepatoma HW-165 in Wistar rats, Biomedicine 34:133–139.PubMedGoogle Scholar
  15. Maia, A. L., Berry, M. J., Sabbag, R., Harney, J. W., and Larsen, P. R, 1995a, Structural and functional differences in the diol gene in mice with inherited type 1 deiodinase deficiency, Mol. Endocrinol. 9:969–980.CrossRefGoogle Scholar
  16. Maia, A. L., Kieffer, J. D., Harney, J. W., and Larsen, P. R, 1995b, Effect of 3,5,3’-Triiodothyronine (T3) administration on diol gene expression and T3 metabolism in normal and type 1 deiodinase-deficient mice, Endocrinology 136:4842–4849.CrossRefGoogle Scholar
  17. Mishkin, S. Y., Pollack, R, Yalovsky, M. A., Morris, R P., and Mishkin, S., 1981, Inhibition of local and metastatic hepatoma growth and prolongation of survival after induction of hypothyroidism, Cancer Res. 41:3040–3045.PubMedGoogle Scholar
  18. Popovici, D., Mihai, N., and Urbanavicius, V., 1980, Abnormalities of oxidative phosphorylation due to excess of deficiency of thyroid hormones, Endocrinologie 18:143–147.PubMedGoogle Scholar
  19. Porter, R. K., Joyce, O. J., Fanner, M. K., Heneghan, R, Tipton, K. F., Andrews, J. F., McBennett, S. M., Lund, M. D., Jensen, C. R, and Melia, H. P., 1999, Indirect measurement of mitochondrial proton leak and its application, Int. J. Obes. Relat. Metab. Disord 23 Suppl. 6:12–18.CrossRefGoogle Scholar
  20. Rashid, A., Wu, T. C., Huang, C. C., Chen, C. R, Lin, H. Z., Yang, S. Q., Lee, F. Y., Diehl, A. M., Gong, D. W., He, Y., and Reitman, M. L., 1999, Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver. Genomic organization and regulation by dietary fat of the uncoupling protein 3 and 2 genes, Hepatology 29:1131–1138.PubMedCrossRefGoogle Scholar
  21. Short, J., Wedmore, R, Kibert, L., and Zemel, R, 1980, Triidothyronine: on its role as a specific epatomitogen, Cytobios. 28:165–177.PubMedGoogle Scholar
  22. Staniek, K., and Nohl, R, 1999, H(2)O(2) detection from intact mitochondria as a measure for one-electron reduction of dioxygen requires a non-invasive assay system, Biochim. Biophys. Acta 1413:70–80.Google Scholar
  23. Wastl, U. M., Rossmanith, W., Lang, M. A., Camus Randon, A. M., Grasl Kraupp, B., Bursch, W., and Schulte Hermann, R., 1998, Expression of cytochrome P450 2M in preneoplastic and neoplastic mouse liver lesions, Mol. Carcinog. 22:229–234.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Monika Chabicovsky
    • 1
  • Katrin Staniek
    • 2
  • Walter Rossmanith
    • 1
  • Wilfried Bursch
    • 1
  • Hans Nohl
    • 2
  • Rolf Schulte-Hermann
    • 1
  1. 1.Institute of Cancer ResearchUniversity of ViennaViennaAustria
  2. 2.lnstitute of Pharmacology and ToxicologyVeterinary University of ViennaViennaAustria

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